Classifications

• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
  • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
  • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
  • G01N33/92—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving lipids, e.g. cholesterol, lipoproteins, or their receptors
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K49/00—Preparations for testing in vivo
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
  • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
  • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
  • A61K8/37—Esters of carboxylic acids
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
  • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
  • A61K8/67—Vitamins
  • A61K8/678—Tocopherol, i.e. vitamin E
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
  • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
  • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
  • A61K8/9783—Angiosperms [Magnoliophyta]
  • A61K8/9789—Magnoliopsida [dicotyledons]
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
  • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
  • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
  • A61K8/9783—Angiosperms [Magnoliophyta]
  • A61K8/9794—Liliopsida [monocotyledons]
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P17/00—Drugs for dermatological disorders
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P17/00—Drugs for dermatological disorders
  • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P17/00—Drugs for dermatological disorders
  • A61P17/16—Emollients or protectives, e.g. against radiation
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P39/00—General protective or antinoxious agents
  • A61P39/06—Free radical scavengers or antioxidants
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
  • A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
  • A61Q17/04—Topical preparations for affording protection against sunlight or other radiation; Topical sun tanning preparations
• • C—CHEMISTRY; METALLURGY
  • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
  • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
  • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
  • C12Q1/02—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving viable microorganisms
  • C12Q1/025—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving viable microorganisms for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
  • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
  • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
  • G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
  • G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
  • G01N33/502—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics for testing non-proliferative effects
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
  • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
  • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
  • G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
  • G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
  • G01N33/5082—Supracellular entities, e.g. tissue, organisms
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
  • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
  • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
  • G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
  • G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
  • G01N33/5082—Supracellular entities, e.g. tissue, organisms
  • G01N33/5088—Supracellular entities, e.g. tissue, organisms of vertebrates
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
  • A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
  • A61K2800/52—Stabilizers
  • A61K2800/522—Antioxidants; Radical scavengers

Definitions

• This invention relates generally to compositions applied topically to skin and hair for protection against ultraviolet radiation.
• the invention also relates to methods of selecting antioxidants for inclusion in such compositions.
• UV radiation ultraviolet radiation
• ROS reactive oxygen species
• EP 1591104 (STADA Pharmaceuticals AG) describes the use of antioxidants in pharmaceutical formulations for protection against infrared radiation.
• Antioxidants function to neutralize ROS. If the right type and level are present within skin where ROS are being formed, Aox should be able to neutralize ROS before they can attack and oxidize other biomoiecules. Accordingly, it would be usefuf to have a method to determine which topical applied antioxidants can be highly effective at neutralizing UVR-induced reactive oxygen species (ROS) within skin. Further, it would be useful to have a method to distinguish compounds which may only be effective in solution to scavenge free radicals from compounds that may be highly effective antioxidants on skin when exposed to UVR.
• ROS UVR-induced reactive oxygen species
• the invention described herein provides, inter alia, a method which comprises two unique ex vivo methods to assess the ability of topically applied Aox to provide protection against UVR-induced ROS formation within skin's outer layers.
• the first method uses microscopy, e.g., fluorescence microscopy, to image and quantify ROS formation in the inner layers of the epidermis, e.g. through to the basal layers, by imaging sections of human skin.
• the second method quantifies the extent to which the Aox containing composition inhibits peroxidation of lipids in skin's outer layers.
• the present invention provides a method for confirming antioxidant activity of a composition formulated for topical application to skin, wherein the method comprises testing the composition for ability to inhibit both ultraviolet radiation- induced lipid peroxidation on skin and ultraviolet radiation-induced reactive oxygen species formation throughout the epidermis.
• the invention also provides a method for screening compounds for antioxidant behavior in a composition to be topically applied to skin, wherein the screening method comprises determining the compound's ability to inhibit both ultraviolet radiation-induced skin lipid hydroperoxide formation and ultraviolet radiation-induced reactive oxygen species formation throughout the epidermis.
• This invention also provides a composition for application to skin or hair of a subject, wherein the composition comprises an antioxidant compound or combination of antioxidant compounds, wherein the antioxidant compound or combination of antioxidant compounds substantially inhibit both ultraviolet radiation-induced skin lipid peroxidation and ultraviolet radiation-induced reactive oxygen species formation throughout the epidermis.
• the invention further provides for a composition for topical application, wherein the composition comprises at least one antioxidant compound that substantially inhibits ultraviolet radiation-induced reactive oxygen species formation in the upper layers of the epidermis and at least one antioxidant compound that substantially inhibits ultraviolet radiation-induced reactive oxygen species formation sn the lower layers of the epidermis.
• Figure 1 - shows the extent to which antioxidants (Aox) inhibit UVR- tnduced formation of lipid hydroperoxides (LOOH) ex vivo using tape strips to collect lipids from human skin in the presence of different types and levels of Aox.
• FIG. 2 - shows that the addition of antioxidants to sunscreens significantly reduces UV-induced formation of ROS within the stratum corneum.
• the SPF 30 sunscreen formula reduced ROS by 39% whereas the SPF 30 formula with 0.5% vitamin E and 0.1% Emblica as antioxidants reduced ROS by 73%.
• the extent of ROS formation is color coded, with blue indicating Sow and orange or red indicating high ROS levels.
• Figure 3 - shows two photon fluorescence microscopy on skin layers to demonstrate ability of Vitamin E and Emblica antioxidants to reduce UV-induced formation of ROS within the epidermis.
• a composition containing 0.5% Vitamin E and 0.1 % Emblica provide little protection against free radical formation in the lower (basal) layer of the epidermis.
• Figure 4 - shows two photon fluorescence microscopy on skin layers to demonstrate effect of various known antioxidants to reduce UV-induced formation of ROS within the epidermis. Tested antioxidant extracts actually increased rather than decreased free radicals when exposed to UVR.
• Figure 5 - shows two photon fluorescence microscopy on skin layers to demonstrate effect of various known antioxidants to reduce UV-induced formation of ROS within the epidermis after 1 MED of UVR.
• a composition containing 0.5% Vitamin E and 0.9% Oxynex ST are shown to inhibit formation of ROS within lower epidermal layers.
• Figure 6 ⁇ shows two photon fluorescence microscopy on skin layers to demonstrate effect of various known antioxidants to reduce UV-induced formation of ROS within the epidermis after 4 MED of UVR, A composition containing 0.5% Vitamin E and 0.9% Oxynex ST are shown to inhibit formation of ROS within lower epidermal layers.
• the present invention provides a method for confirming antioxidant activity of a composition formulated for topical application to skin, wherein the method comprises testing the composition for ability to inhibit both ultraviolet radiation- induced lipid peroxidation on skin and ultraviolet rad ⁇ at ⁇ on-induced reactive oxygen species formation throughout the epidermis.
• the invention also provides a method for screening compounds for antioxidant behavior in a composition to be topically applied to skin, wherein the screening method comprises determining the compound's ability to inhibit both ultraviolet radiation-induced skin lipid hydroperoxide formation and ultraviolet radiation-induced reactive oxygen species formation throughout the epidermis.
• determining inhibition of ultraviolet radiation-induced reactive oxygen species formation in the skin comprises imaging skin throughout the epidermis down to the basal layer using two-photon fluorescence intensity imaging.
• determining inhibition of UVR-induced skin lipid hydroperoxide formation comprises determining percent lipid hydroperoxide inhibition of the compound in comparison to placebo.
• the methods of the invention comprise the steps of applying to distinct areas of skin of a subject an antioxidant containing composition and a placebo composition to produce an antioxidant skin site containing antioxidant and skin lipids and a placebo skin site containing placebo and skin lipids; applying a strip to the antioxidant skin site and the placebo skin site to produce an antioxidant strip sample containing antioxidant and skin lipids and a placebo strip sample containing placebo and skin lipids; removing said strip samples from the skin and exposing said strip samples to UVR to form a UVR- induced antioxidant/lipid reaction product on the antioxidant strip sample and a UVR-induced piacebo/lipid reaction product on the placebo strip sample; separately contacting the antioxidant strip sample and the placebo strip sample with solvent to prepare a first extract containing UVR-induced antioxidant/fipid reaction product and a second extract containing UVR-induced placebo/iipid reaction product; assaying said first and second extracts for lipid hydroperoxide content for each extract; and comparing the lipid hydroperoxide content of the first extract to the lipid hydro
• the methods of the invention comprise the further steps of applying placebo to two distinct sites on the skin of the subject; producing strip samples from each site; subjecting strip samples from only one of the two placebo sites to UVR to produce a subset of irradiated placebo strip samples and a subset of nonirradiated placebo strip samples; separately contacting nonirradiated placebo strip samples with solvent to prepare a third extract containing p ⁇ acebo and skin lipids; and assaying said third extract for lipid hydroperoxide content to determine background lipid hydroperoxide formation.
• the methods of the invention comprise comparing the iipid hydroperoxide content of the first extract to the lipid hydroperoxide content of the second extract comprises calculating percent iipid hydroperoxide formation by the following formula:
• %LF is the percent Iipid hydroperoxide formation
• LOOH 1 is the Iipid hydroperoxide content of the first extract
• LOOH2 is the Iipid hydroperoxide content of the second extract
• LOOH3 is the Iipid hydroperoxide content of the third extract.
• antioxidant refers to compounds or combinations of compounds determined by the methods of the invention to have a %LF that is less than 100%.
• prooxidant refers to compounds or combinations of compounds that have a %LF that is greater than 100%.
• certain compounds referred to in the art as antioxidants actually have a prooxidant behavior when tested according to the methods of the invention, making them unsuitable as ingredients in compositions for topical application, particularly in sunscreens, unless present in the combinations as described herein.
• compositions of the invention containing the appropriate Aox can comprise any form readily known by those of ordinary skill in the art of preparing cosmetic compositions. Examples of such include, but are not limited to, nonionic vesicle dispersions, emulsions, creams, milks, gets, cream gels, ointments, suspensions, dispersions, powders, solids, sticks, foams or sprays.
• the composition can comprise an anhydrous or aqueous 5 solid or paste, emulsion, suspension, or dispersion.
• Preferable forms of the compositions include an oil-in-water emulsion, a water-in-oil emulsion, an alcohol solution, or an aerosol formulation.
• the subject invention also provides a cosmetic composition for topical application to human skin and/or hair, comprising an appropriate Aox and amount i o of Aox determined by the methods described herein.
• cosmetic compositions may include such products as moisturizers, cleansers, conditioners, shampoo, body wash, styling gei/lotion, eye cream and eye liner, blush, mascara, foundation, nail polish, polish remover, eye shadow, lipstick, iip gloss, lip liners, lip balms, makeup remover, nail treatment, foot care is compositions, acne treatment, redness/rosacea treatment, varicose/spider vein treatment, anti-aging compositions, sunless tanning compositions, after-sun compositions, concealers, hair color and bleaching compositions, skin fading/lighteners, body firming lotion, shaving cream, after shave, refaxer, antiperspirants and deodorants, exfoHants, scrubs, liquid hand soap, bubble bath,
• antioxidants useful in the compositions of the invention include, but are not limited to, D ⁇ ethylhexyl syringylidene maionate, Vitamin E, diisopropyl vanillidene maionate (also referred to as DiPVM) and related compounds (described in U.S. Patent Nos.
• antioxidants to be added to the compositions of the invention are generally between about 0,01 % by weight to about 10.0% by weight, preferably between about 0.1% by weight to about 5.0% by weight. Exact amounts can be determined by one of ordinary skill in the art according to testing methods described herein.
• composition of the invention can comprise
• composition of the invention may comprise Vitamin E in combination with a pro-oxidant compound as determined by the methods of the invention, where the presence of Vitamin E in these embodiments will counteract the pro-oxidant effects of these compounds to form an antioxidants combination, in certain embodiments of this composition Vitamin E is present in an amount greater than about 0.05% by weight, in an amount of about 0.1% by weight or greater, in an amount of about 0.25% by weight or greater, and in an amount of about 0.5% by weight or greater.
• pro-oxidant compounds that will be useful in the compositions of the invention that comprise0 Vitamin E include, but are not limited to, Rosemary officinalis oleorestn, Rosa Gallica extract, Bioactive Photosynthetic complex from green plants, Thermus Thermophiilus ferment, ergothiotaine and combinations thereof.
• Amounts of pro- oxidants to be added to the compositions of the invention are generally between about 0.01 % by weight to about 10.0% by weight, preferably between about 0.1% 5 by weight to about 5.0% by weight. Exact amounts can be determined by one of ordinary skill in the art according to testing methods described herein,
• the composition can be in the form of an aerosol, wherein the composition is combined with at least one o propeilant.
• o propeilant which may be any suitable gas that can be compressed or liquefied within a spray dispensing canister and which expands or volatilizes to vapor or gas form upon exposure to ambient temperature and pressure conditions to deliver the composition in an aerosol form.
• Suitable propeilants include hydrocarbons having 1 to 5 carbon atoms, including but not limited to methane, ethane, propane, tsopropane, butane, isobutane, butene, pentane, isopentane, neopentane, pentene, hydrofluorocarbons (HFCs), chforofluorocarbons(CFCs), nitrogen, ethers including dimethyl ether, and any mixtures thereof.
• hydrofluorocarbons HFCs
• CFCs chforofluorocarbons
• the composition in the aerosol container is liquid formulation which can contain dissolved propellant, undissoived liquid propel ⁇ ant and gaseous propellant. Ail of this is under pressure due to the vapor pressure of the prope ⁇ ant.
• the propeilant can be present in an amount up to about 90 weight percent, preferably from about 2 weight percent to about 50 weight percent, and more preferably about 5 weight percent to about 40 weight percent, most preferably 30 weight percent, based on the total weight of the aerosol composition.
• the compositions of the invention can also comprise aerosol foams or so- calted mousse compositions.
• 6,627,585 describes a mousse-forming cleansing shampoo composition
• a foamable concentrate comprising at least one surfactant, dispersed particles of a water- insoiuble conditioning agent, an aqueous carrier; and an aerosol propellant.
• U.S. Patent No. 6,264,964 describes a cosmetic composition including a crosslinked non-emulsifying poiys ⁇ oxane elastomer and a carboxyvinyl polymer which is in the form of an aerosol foam in a pressurized system, The propeiiant may be introduced into the mousse composition at the time of filling by using a standard aerosol dispenser, e.g. a spray can arrangement.
• compositions of the present invention may contain a wide range of additionaf, optional components which are referred to herein as "cosmetic components", but which can also include components generally known as pharmaceutically active agents.
• Cosmetic components optional components which are referred to herein as "cosmetic components”
• CTFA Cosmetic Ingredient Handbook Seventh Edition, 1997 and the Eighth Edition, 2000, which is incorporated by reference herein in its entirety, describes a wide variety of cosmetic and pharmaceutical ingredients commonly used in skin care compositions, which are suitable for use in the compositions of the present invention.
• Examples of these functional classes disclosed in this reference include: absorbents, abrasives, anticaking agents, antifoaming agents, antioxidants, binders, biological additives, buffering agents, bulking agents, chelating agents, chemical additives, colorants, cosmetic astringents, cosmetic biocides, denaturants, drug astringents, external analgesics, film formers, fragrance components, humectants, opacifying agents, pH adjusters, plasticizers, reducing agents, skin bleaching agents, skin- conditioning agents (emollient, hurnectants, miscellaneous, and occlusive), skin protectants, solvents, foam boosters, hydrotropes, soiubilizing agents, suspending agents (nonsurfactant), sunscreen agents, ultraviolet light absorbers, SPF boosters, waterproofing agents, and viscosity increasing agents (aqueous and nonaqueous).
• the composition may contain one or more sunscreen active agents.
• sunscreen active agent or “sunscreen active” shall include all of those materials, singly or in combination, that are regarded as acceptable for use as active sunscreening ingredients based on their ability to absorb UV radiation.
• Such compounds are generally described as being UV-A, UV-B, or UV-A/UV-B active agents. Approval by a regulatory agency is generaliy required for inclusion of active agents in formulations intended for human use.
• Those active agents which have been or are currently approved for sunscreen use in the United States include organic and inorganic substances including, without limitation, para aminobenzoic acid, avobenzone, cinoxate, dioxybenzone, homosalate, menthyl anthranilate, octyl salicylate, oxybenzone, padimate O, phenylbenzimidazole sulfonic acid, sulisobenzone, troiamine salicylate, titanium dioxide, zinc oxide, diethanolamine methoxycinnamate, digafloy trioleate, ethyl dihydroxypropyl PABA, glyceryl aminobenzoate, iawsone with dihydroxyacetone, red petrolatum.
• organic and inorganic substances including, without limitation, para aminobenzoic acid, avobenzone, cinoxate, dioxybenzone, homosalate, menthyl anthranilate, octyl salicylate, oxybenzone, padi
• the additional sunscreen active agent comprises a photoprot ⁇ cting effective amount of particulates of at least one inorganic pigment or nanopigment, non-limiting examples of which include titanium dioxide, zinc oxide, iron oxide, zirconium oxide, cerium oxide, or mixture thereof.
• the compositions of the invention may also include materials that also increase the SPF of the final composition by such mechanisms as UV radiation scattering and dispersion.
• UV-radiation scattering agents comprise materials that exhibit UV absorbing activity or exhibit no UV absorbing activity.
• An example of such UV-radiation scattering agents include polymeric materials, such as the product known as SunSpheresTM (Rohm and Haas; Philadelphia, PA) which are described by their manufacturer as hollow styrene/acryiates copolymer spheres manufactured by emulsion polymerization. The polymer spheres are said to raise SPF values across the UVA and UVB region by dispersing and/or scattering the incident UV radiation throughout the film of sunscreen present on a surface, such as human skin.
• the spheres cause less UV radiation to penetrate into the skin by redirecting the radiation towards the UV-absorbing sunscreen actives in the sunscreen formulation, where the radiation reacts with the sunscreen active molecules and the energy is dissipated as heat
• the terms "spheres” or “scattering agents” are not limited by chemical makeup or shape, but comprise any agent that produces the effect of lengthening the path of incident UV radiation, increasing the statistical likelihood that the radiation will contact a sunscreen active molecule, i.e., a UV absorbing active agent.
• UV absorbing materials may also include UV absorbing materials that also exhibit scattering properties such as ZnO (examples include Z-CoteTM products available from BASF), ⁇ O2 (examples include the Solave ⁇ TM products available from Uniqema (New Castie, DE, USA)), compounds such as methylene bis-benzotriazofyl tetramethylbutylphenol, (TinasorbTM M" available from Ciba Specialty Chemicals, inc. (Basel, Switzerland ).
• UV radiation scattering agents are typically present in the formulation in amounts up to about 10% by weight, preferably in ranges of about 0,5% to about 7.0% by weight, in particularly preferred ranges of 3% to about 5% by weight.
• sunless-tanning agent or “self-tanning compositions” refer to compositions which, when applied to human skin, impart thereto an appearance similar to that achieved by exposing the skin to naturai or artificial sunlight.
• sunless tanning active agents are described in U.S. Patent Nos. 6,482,397, 6,261,541, and 6,231,837.
• Such sunless tanning compositions typically comprise, in addition to an artificial tanning effective amount of a self tanning agent, effective amounts of a composition coloring agent and a cosmetically acceptable carrier adapted for topical application to human skin.
• the self tanning agents can also include those compositions generally accepted in the art for application to human skin, and which, when so applied, react therein with amino acids so as to form pigmented products. Such reactions give the skin a brown appearance similar to the coior obtained upon exposing it to sunlight for periods of time sufficient to tan the skin.
• Suitable self tanning agents include, without limitation, alpha-hydroxy aldehydes and ketones, glyceraldehyde and related alcohol aldehydes, various indoles, imidazoles and derivatives thereof, and various approved pigmentation agents.
• Presently preferred herein as self tanning agents are the alpha-hydroxy aldehydes and ketones. Most preferably, the self tanning agent is dihydroxyacetone ("DHA").
• Suitable self tanning agents include, without limitation, methyl glyoxal, glycerol aldehyde, erythrufose, alloxan, 2,3-dihydroxysuccindiafdehyde. 2,3- dimethoxysuccindialdehyde, 2 ⁇ amtno-3-hydroxy ⁇ succindialdehyde and 2- benzylamino-3-hydroxysuccindiaidehyde.
• Suitable emulsifiers or surfactants include pharmaceutically acceptable, non-toxic, non-ionic, anionic and cationic surfactants.
• suitable non- ionic surfactants include glycerol fatty acid esters such as glycerol monostearat ⁇ , glycol fatty acid esters such as propylene glycol monostearate, polyhydric alcohol fatty acid esters such as polyethylene glycol (400) mono ⁇ leate, polyoxyethylene fatty acid esters such as polyoxyethylene (40) stearate, polyoxyethylene fatty alcohol ethers such as po ⁇ yoxyethylene (20) stearyl ether, polyoxyethylene sorbitan fatty acid esters such as polyoxyethylene sorbitan monostearate, sorbitan esters such as sorbitan monostearate, alkyl glycosides such as cetearyl giucoside, fatty acid ethanolamides and their derivatives such as the diethan ⁇ lamide of stearic acid, and the like.
• Suitable anionic surfactants are soaps including alkali soaps, such as sodium, potassium and ammonium salts of aliphatic carboxylic acids, usually fatty acids, such as sodium stearate.
• Organic amine soaps include organic amine salts of aliphatic carboxylic acids, usually fatty acids, such as triethanolamine stearate.
• Metallic soaps include salts of polyvalent metals and aliphatic carboxylic acids, usually fatty acids, such as aluminium stearate.
• Suitable anionic surfactants include sulfated fatty acid alcohols such as sodium lauryl sulfate, sulfated oils such as the sulfuric ester of ricino!eic acid disodium salt, and sulfonated compounds such as alkyl sultanates including sodium cetane sulfonate, amide sulfonates such as sodium N-methyl-N-oleyl laurate, sulfonated dibasic acid esters such as sodium dioctyl sulfosuccinate, aikyl aryl sulfonates such as sodium dodecylbenzene sulfonate, alkyl naphthalene sulfonates such a sodium isopropy!
• naphthalene sulfonate petroleum sulfonate such as aryi napthalene with alkyl substitutes.
• suitable cationic surfactants include amine salts such as octadecyi ammonium chloride, quartemary ammonium compounds such as benzalkonium chloride.
• An emollient is an oleaginous or oily substance which helps to smooth and soften the skin, and may also reduce its roughness, cracking or irritation.
• suitable emollients include mineral oil having a viscosity in the range of 50 to 500 centipotee (cps), ianolin oil, coconut oil, cocoa butter, ofive oif, almond oil, macadamia nut oil, aloe extracts such as aloe vera lipoquinone, synthetic jojoba oils, natural sonora jojoba oils, safflower o ⁇ i, corn oil, liquid lanolin, cottonseed oil and peanut oil.
• cps centipotee
• the emollient is a cocoglyceride, which is a mixture of mono, di- and triglycerides of cocoa oil, sold under the trade name of Myrito! 331 from Henkel KGaA, or D ⁇ caprylyl Ether available under the trade name Cetiol OE from Henkel KGaA or a C1 2 -C15 Alkyl Benzoate sold under the trade name Finsoiv TN from Finetex.
• One or more emollients may be present ranging in amounts from about 1 percent to about 10 percent by weight, preferably about 5 percent by weight.
• Another suitable emollient is DC 200 Fluid 350, a silicone fluid, available Dow Coming Corp.
• emollients include squalane, castor oil, polybutene, sweet almond oil, avocado oil, calophyilum oil, ricin oil, vitamin E acetate, olive oil, silicone oiis such as dimethylopolysiioxane and cyciomethicone, iinolenic alcohol, oteyl aicohol, the oil of cereal germs such as the oii of wheat germ, isopropyl paimitate, octyi patmitate, isopropyl myristate, hexadecy!
• emollients which are solids or semi-solids at ambient temperatures may be used.
• Such solid or semi-solid cosmetic emollients include glyceryl d ⁇ iaurate, hydrogenated lanolin, hydroxylated lanolin, acetyiated lanolin, petrolatum, isopropyl lanolate, butyl myristate, cetyl myristate, myristy! myristate, myristyl lactate, cetyl alcohol, isostearyi alcohol and isocetyl lanoiate.
• One or more emollients can optionally be included in the formulation.
• a humectant is a moistening agent that promotes retention of water due to its hygroscopic properties.
• Suitable humectants include glycerin, polymeric glycols such as polyethylene glycol and polypropylene glycol, mannitol and sorbitol.
• the humectant is Sorbitol, 70% USP or polyethylene glycol 400, NF.
• One or more humectants can optionally be included in the formulation in amounts from about 1 percent to about 10 percent by weight, preferably about 5 percent by weight.
• a dry-fee! modifier is an agent which when added to an emuteion, imparts a
• Dry feel modifiers can include talc, kaolin, chalk, zinc oxide, silicone fluids, inorganic salts such as barium sulfate, surface treated silica, precipitated silica, fumed silica such as an Aerosi! available from Degussa Inc. of New York, N. Y. U.S.A.
• Another dry feel modifier is an epichlorohydrin cross-linked glyceryl starch of the type that is disclosed in U.S. Patent No. 6,488,916.
• additional thickening agents such as, for instance, various Carbopols available from Noveon Co. Particularly preferred are those agents which would not disrupt the lamellar structure in the formulation of the final product, such as non-ionic thickening agents.
• additional thickening agents is well within the skill of one in the art.
• Additional natural or synthetic substances can also added to the compositions of the invention to protect from or delay its deterioration due to the action of oxygen in the air (oxidation). They may also reduce oxidation reactions in skin tissue. Such substances prevent oxidative deterioration which may lead to the generation of rancidity and nonenyzymatic browning reaction products. Typical suitable substances include propyl, octyl and dodecy!
• esters of gallic acid butylated hydroxyanisole (BHA, usually purchased as a mixture of ortho and meta isomers), butylated hydroxytoluene (BHT), green tea extract, uric acid, cysteine, pyruvate, nordihydroguaiaretic acid, Vitamin A, Vitamin E and Vitamin C and their derivatives.
• BHA butylated hydroxyanisole
• BHT butylated hydroxytoluene
• green tea extract green tea extract
• uric acid cysteine
• pyruvate pyruvate
• nordihydroguaiaretic acid Vitamin A
• Vitamin E and Vitamin C and their derivatives can optionaify be included in the composition in an amount ranging from about 0.001 to about 5 weight percent, preferably about 0.01 to about 0.5 percent.
• Chelating agents are substances used to chelate or bind metallic tons, such as with a heterocyiic ring structure so that the ion is held by chemical bonds from each of the participating rings.
• Suitable chelating agents include ethylene diaminetetraacetic acid (EDTA), EDTA disodium, calcium disodium edetate, EDTA trisodium, albumin, transferrin, desferoxamine, desferal, desferoxamine mesylate, EDTA tetrasodium and EDTA dipotassium, or combinations of any of these.
• Fragrances are aromatic substances which can impart an aesthetically pleasing aroma to the sunscreen composition.
• Typical fragrances include aromatic materials extracted from botanical sources (i.e., rose petals, gardenia blossoms, jasmine flowers, etc.) which can be used alone or in any combination to create essential oils.
• alcoholic extracts may be prepared for compounding fragrances.
• One or more fragrances can optionally be included in the sunscreen composition in an amount ranging from about 0.001 to about 5 weight percent, preferably about 0.01 to about 0.5 percent by weight.
• Additionat preservatives may aiso be used if desired and include well known preservative compositions such as benzyl alcohol, phenyl ethyl alcohol and benzoic acid, diazolydinyl, urea, chlorphenesin, iodopropynyl and butyl carbamate, among others.
• compositions of the invention can further comprise skin protectant active agents. Suitable examples include (with preferred weight percent ranges), Allantoin (0.5 to 2 percent); Aluminum hydroxide gel (0.15 to 5 percent); Calamine
• Hard fat greater than 50
• Kaolin ⁇ 4 to 20 percent
• Lanolin (12.5 to 50 percent);
• Mineral oil greater than 50 percent
• Petrolatum greater than 30 percent
• Sodium bicarbonate Topical starch (10 to 98 percent);
• White petrolatum greater than 30 percent
• Zinc acetate 0.1 to 2 percent
• Zinc carbonate 0.2 to 2 percent
• Zinc oxide 1 to 25 percent
• compositions of the invention may further include insect repelling components.
• insect repelling active agent for personal care products is N.N-Dtethyl-m-toluamide, frequently called "DEET" and available in the form of a concentrate containing at least about 95 percent DEET.
• Other synthetic chemical repellents include ethy) butylacetylaminoproprionate (also known as IR 3535), dimethyl phthalate, ethyl hexanediol, indaione, di-n- propylisocinchoronate, bicycioheptene, dicarb ⁇ ximlde and tetrahydrofuraldehyde.
• Certain plant-derived materials also have insect repellent activity, including citronella oil and other sources of citronella (including lemon grass oil), iimonene, rosemary oil and eucalyptus oil.
• Choice of an insect repellent for incorporation into the sunscreen emulsion will frequently be influenced by the odor of the repellent.
• the amount of repelfent agenl used will depend upon the choice of agent; DEET is useful at high concentrations, such as up to about 15 percent or more, while some of the plant-derived substances are typically used in much lower amounts, such as 0.1 percent or less.
• Topical application of the compositions of the invention described herein to the hair or skin of a human will provide enhanced protection against deleterious effects of ultraviolet radiation (UVR).
• UVR ultraviolet radiation
• the subject invention further provides a method for protecting human skin and/or hair against the deleterious effects of solar radiation, more particularly UVR, which method comprises topically applying thereto an effective amount of the compositions as described herein containing sunscreens and one or more antioxidants.
• An esthetically beneficial result of exposure of skin to UVR i.e., light radition wavelengths of from 280 nm to 400 nm
• UVR is typically divided into UV-A (light wavelengths from 320 to 400 nm) and UV-B (wavelengths ranging from 280 to 320 nm) regions.
• Overexposure to UV-B irradiation is generally understood to lead to skin bums and erythema.
• overexposure to UV-A radiation may cause a loss of elasticity of the skin and the appearance of wrinkles, promoting premature skin aging.
• Such irradiation promotes triggering of the erythema! reaction or amplifies this reaction in certain individuals and may even be the source of phototoxic or photoaliergic reactions.
• overexposure to UV-A may also lead to melanoma.
• the application of the compositions of the invention to the skin and/or hair of an individual will provide enhanced UVR photo protection (UV-A and/or UV-B) of the skin and/or hair of the individual.
• the invention further provides a method of treating and/or reversing photodamage of skin by applying the compositions of the invention to skin that will be or has been exposed to UVR.
• the term "treating and/or reversing photodamage” is intended to mean obtaining an improvement in one or more attributes of skin condition such as dryness, texture, elasticsty/firmness/ressliency, Sines/wrinkles, skin tone/clarity, uniformity of pigmentation, and/or erythema which condition is exacerbated by exposure to UVR.
• the sunscreen containing compositions of the invention are intended to provide a sun protection factor (SPF) rating of at least 2, with additional preferable embodiments having a sun protection factor of at least 5, at least 10, at least 15, at least 20, at ieast 25, at least 30, at least 35, at least 40, at least 45, at least 50 s at least 55, at least 60, at least 65, at least 70, at least 75, at least 80, at least 85 S at least 90, at least 95, and at least 100.
• the sunscreen containing compositions of the invention are also intented to provide U.S. FDA UV-B "star ratings" of at least one star, at least two stars, at least three stars and up to four stars.
• DPPH is a stable free radical that when dissolved in solution forms an intense purple color. When reduced by an antioxidant, the purple color fades until it finally disappears as DPPH is completely reduced. The extent to which the color fades can be easily measured and used to rank the relative effectiveness of different materials purported to have antioxidant properties. o Measurements were recorded for antioxidant raw materials in simple methanol solutions. Samples were prepared by dissolving antioxidants at various concentrations in methanol. After sample preparation, 125 ⁇ l of the sample or pure methanol as a contra! were pipetted into sample test tubes followed by 2 ml of methanol and vortexed.
• ARU (Absorbance Methanol Control - Absorbance sample) X 10
• ARU values range in magnitude from 0 for "no" efficacy to about 15 for raw materials that have high antioxidant efficacy.
• Antioxidant effectiveness for a variety of oil and water-solub ⁇ e raw materials purported to have antioxidant properties appears in Table 1.
• the raw materials include well-known antioxidants such as vitamin E, in addition to popular plant extracts such as green tea, rose, grape and mushrooms, among others. Effectiveness is expressed as antioxidant reducing units (ARU), which span values of 0 for no efficacy to 12 for antioxidants with high efficacy to reduce the DPPH radical. Examples of both oi! and water soluble antioxidants spanned this range.
• antioxidants with ARU > 6.5 would be superior to vitamin E in their ability to neutralize UVR-induced formation of ROS within the skin.
• ROS covers a wide range of reactive compounds, including free radicals but also other oxidants like hydrogen peroxide, singlet oxygen or peroxy nitrite, results from the DPPH free radical test may not adequately predict antioxidant effectiveness on skin that is exposed to UVR.
• antioxidants that maintain their effectiveness on skin in the presence of UVR 1 we devised a novel and more relevant mode! that utilizes human skin lipids as substrates for UVR-induced peroxidation. Lipids removed from skin on broad pieces of tape serve as the substrates for subsequent exposure to UVR.
• skin lipids can be collected on tape strips in the presence or absence of Aox that essentially maintains the same proximity that ⁇ pids and Aox had on skin.
• the extent to which the presence of Aox protect lipids against peroxidation from ROS can be measured relative to lipids in the absence of antioxidants.
• either placebo or antioxidant lotion was applied (100 mg) to a delineated site on a forearm. Care was taken to insure that products were applied evenly within the entire application area. After application, sites were allowed to air-dry for 30 minutes during which subjects were instructed not to allow any clothing to come into contact with test areas.
• each site was tape-stripped using a 4.0 inch piece of Scotch ⁇ Brand No. 800 Prescription Label tape (1.5 inches wide). One end of the tape was folded over to provide an edge that did not adhere to skin for easy removal. The piece of tape was positioned over a site and then using a finger the tape was gently pressed onto the skin to make good contact. Then the tape was quickly removed from the subject's arm. After removal, all tapes were stored in a dark location such as a drawer until they were either irradiated with UV or extracted with isopropanoi (i.e., non irradiated control).
• Each tape extract was assayed for total LOOH content using a Lipid Hydroperoxide Assay Kit (Kamiya Biomedica ⁇ Company.Thousand Oaks, CA)5 following manufacturer's directions. Lipid hydroperoxides were then quantitated by measuring methylene blue formation at 675 nm using a spectrophotometer. Standard curves were prepared using cumene hydroperoxide and were linear over the range of LOOH detected in these experiments. Each extract was assayed in triplicate and the results presented here represent the mean of those 0 analyses. The standard deviations were typically less than 10%.
• Vitamin E protects skin lipids in a dose dependant manner (yellow bars). Tetrahydrocurcurminoids (THC) are as efficacious as Vitamin E. Vitamin E in combination with Embiica, GT or THC (orange bars) protect about as well as Vit. E alone (yellow bars).
• UV-induced reactive oxygen species ROS
• Test formulas were applied to the surface of skin samples at 2 mg/cm 2 using the tip of a glass rod.
• DHR dshydrorhodamine
• Vitamin E is highly effective at neutralizing UV-induced ROS in the outer layer of epidermis, the stratum corneum. Placebo and experimental formulations were prepared to compare the formulations' ability to inhibit lipid peroxidation. The formulations used are shown in Table 2.
• the formulations were prepared by adding sodium cetearyi sulfate to the water of part A and mixing, followed by addition of either Simulgel NS or Septgel 305 and mixing thoroughly. Then the Part B ingredients were added with mixing, followed by Germaben Il in Part C. After all ingredients are added, the emulsion was mixed thoroughly.
• composition containing vitamin E, by itseff or in combination with Embiica was found to be highly effective at protecting skin's lipids on its outer surface from UV-ind ⁇ ced oxidation mediated by ROS (Tab ⁇ e 3).
• the fluorescence is subsequently detected and quantified to provide an indication of the level of UV-induced ROS formed in deeper layers of the skin
• a water phase was created by adding Acrylates/C 10-30 Alky! Acrylate Crosspoiymer to water of Part A while stirring and mixed until clear and lump-free. While mixing, the propylene glycol and disodium EDTA were added to the water phase mixture of Part A and mixed well for 10 minutes. Triethanolamine of Part B was then added to the water phase mixture and continued mixing well. Separately an oil phase was created by mixing the ingredients of Part C together and heat to 140-145 °F while mixing well. The oil phase was then added to the water phase and continued mixing to form an emulsion. The emulsion was cooled to room temperature and then benzyl alcohol of part D was added to the cool emuis ⁇ o ⁇ and mixed thoroughly. Additions! water was added QS to wesght The difference between the piacebo and experimental formulation was the addition of antioxidants into the oil phase.
• a water phase was created by adding Acrylates/C 10-30 Afky! Acrylate Crosspoiymer to water of Part A while stirring and mixed until clear and lump-free. While mixing, the propylene glycol and disodium EDTA were added to the water phase mixture of Part A and mixed weSi for 10 minutes. Triethanoiamine of Part B was then added to the water phase mixture and continued mixing well. Separately an oil phase was created by mixing the ingredients of Part C together and heat to 140-145 0 F while mixing well. The oil phase was then added to the water phase and continued mixing to form an emulsion. The emulsion was cooied to room temperature and then benzyl alcohol of part D was added to the cool emulsion and mixed thoroughly.
• Oxynex ® ST were also tested in the lipid peroxidation tests described above and shown to prevented UV-rnduced lipid peroxidation by 75%. This is comparable to results obtained for 0.5% Vitamin E plus 0.1 % Embfica. However, although the compositions were similar in ability to inhibit lipid peroxidation, by combining Vitamin E with Qxynex ® ST we have observed an unexpected increase in protection from ROS formation across the ful! thickness of epidermis.
• a clinical efficacy evaluation was conducted to determine the effect of the high SPF antioxidant formulations produced as described above on various indications of skin health including, skin dryness (moisture), skin texture (roughness, smoothness), elasticity (i.e., firmness or resiliency), skin tone and clarity, uniformity of pigmentation, fine lines and wrinkles, erythema, photodamage, and hidden damage (subciinicai pigmentation).
• the study is a single-blind, parallel, randomized, controlled, twelve (12) week use test with an additional baseline equilibration period of seven (7) days.
• One-hundred-nine (109) subjects were enrolled and one-hundred-five (105) continued on the study.
• Four (4) subjects were discontinued due to inability to make ail regularly scheduled visits. No adverse experiences have been reported.
• the results below demonstrate significant improvement over baseline condition of the skin as a result of 12 weeks of use of the tested products.
• Qualified subjects were divided into two (2) product groups and an untreated control group.
• An expert clinical evaluator graded the face of each subject at each visit to assess individual parameters that contribute to the visual and tactile properties of premature aging, as well as to provide an overall global assessment of degree of visible photodamage.
• the clinical grading scores at baseline were used to confirm that the subject presents with mild to moderate photo-damage and therefore were qualified for participation, Specific attributes were quantified using btoinstrumentat ⁇ on; silastic resin replicas with image analysis to also measure fine ⁇ ines and wrinkles, a Nova Meter for determining moisture content, and a Dermalab suction device to measure skin elasticity.
• a trained photographer photographed each subject ai baseline, 2, 4, 8 and 12 weeks using a fixed angle standard and cross-poiarized light Canfield ciinical camera apparatus to document appearance of a specific site on the side of the face (including crow's feet area).
• the photographer took full facial UV reflected photographs, at baseline and at the 12-week visit or until the product had washed out and no longer fluoresces (whichever was later).
• the expert clinical evaiuator graded the UV photographs taken at baseline and 12-weeks ( ⁇ days to washout) to assess degree of subclinical "hidden" damage present and then giobafiy assessed the amount of change compared to baseline.
• Test compositions were overwrapped to hide the identity of the 5 manufacturer and labeled with the appropriate test article codes and use directions. Approximately one-half the study product was delivered prior to the start of the study and the second half of the product was delivered prior to the mid-point of the study.
• subjectsC underwent a baseline equilibration period, during which they discontinued the use of at! facial sunscreens, skin treatment products, their current facial cleansing bar or cream, and any moisturizing facial cosmetic products; use Camay soap daily, each morning for any facial cleansing and as needed throughout the day; and refrain from use of tanning beds for the duration of the study.
• subjects were qualified by presenting with sufficient signs of dryness and extrinsic skin aging. Following qualification, subjects were randomly assigned to one of two test groups or to the untreated control group. For the duration of the study subjects assigned to both the treatment and non-treatment groups wash their faces only with the Camay soap o provided. Subjects in both of the treatment groups applied the assigned test article to their face (and neck if desired) once daiiy (each morning), then reapply as needed.
• Subjects recorded application times each day on a diary provided by the study site at each visit. Subjects in the non-treatment group recorded the number 5 of times that they cleanse and apply their usual moisturizer sunscreen and color cosmetic products during the study. Diaries were collected and redistributed in the same manner as outlined for the treatment groups.
• Subjects were given grades of 0- 4 as follows: 0 normal skin; no signs of dryness 1 mi ⁇ d dryness; slight but definite dryness, fine scaling present may have a powdery or ashy appearance
• Subjects were graded from a score of 0, indicating no lines or wrinkles, to 10 indicating coarse skin containing numerous wrinkles. The results were as follows;
• Facial skin condition was measured on all subjects using Dermalab, Novameter and replica image analysis at baseline and weeks 2, 4, 8 and 12 as follows.
• o Elasticity was measured on one side of the face (same location at each visit) on all subjects using the Dermalab (Cortex Technology, Denmark), which applies a negative pressure to the skin surface and calculates the height to which the skin can be drawn up and the rate at which it returns to equilibrium thus providing a measurement of elasticity. Dermalab measurements took place on5 the opposite side of the face as image analysis replicas.
• M ⁇ isturization was measured on one side of the face (same location at each visit) io document hydration levels of the skin surface. The relative degree of skin hydration is assessed using the Derma! Phase Meter 9003 (NOVA meter). Measurements are made by applying an alternating voltage to the skin with a c ciosely spaced pair of electrodes and measuring the impedance. Changes in water content change the impedance of the capacitive circuit. The first two consecutive readings within 10% were recorded. The same side of the face is measured at each visit. The test room temperature and humidity will be recorded during each set of readings.
• Contour (surface textural) analysis provides a method for quantifying skin augmentation, the cosmetic action of reducing lines and wrinkles.
• skin replicas made of the crow's feet area were analyzed for contour and surface texture using image analysis.
• Skin replicas of the crow's feet area were prepared using silastic resin impression materials (Cuderm).
• Silastic resin is a rapidly curing liquid applied using 1cm diameter replica rings which stay intact after application and removal, Facial skin condition was documented for ail subjects using standard and cross polarized light photography at baseline and weeks 2, 4, 8 and 12.
• Hidden damage accumulated betow the skin surface was evaluated by expert graders, based on UV photos taken at baseline and 12-weeks.
• Digital photographs using both visible and cross-polarized light are taken of all subjects at all visits.
• Subjects' faces are positioned in the Canfield stereotactic repositioning apparatus and photographs are taken using the Canfield Clinical Systems camera and flash system.
• the camera used was a Nikon D80 SLR 35 mm model with a 60 mm macro Nikkor lens and a modified S8-23 flash head.
• the camera is set in Aperture priority automatic at f 16.
• a slate was photographed at 1 :6 magnification identifying the subject and time interval.
• a frontal photo was taken at 1 :6 magnification and two lateral 45 ° angle photos of each side of the face is taken at 1 :4 and 1 :3 magnification using standard lighting and repeated using cross-polarized light.
• the camera used was a Nikon 6006 SLR 35 mm model.
• a slate was photographed at 1 ;6 magnification identifying the subject and time interval.
• a frontal photo was taken at 1 :6 magnification and one lateral 45 " angle photo of each side of the face was taken at 1:6 magnification.
• two frontal UV-light (UV reflected) photographs were taken at 1 :6 magnification employing a Kodak 18A filter over the lens, a Sunpak SVIS 4000 Monolight and T-Max 400 black and white print film.
• Exposures were taken at f8 and 1/250 sec, shutter speed.
• An expert evaluator graded full facial photos individually for uniformity of pigmentation at each time-point (baseline and 12-week) grading on a scale of 0 ⁇ uniform/even) to 10 (uneven, blotchy mottled).
• the expert evaiuator also conducted a comparative assessment of 12-week photos vs. baseline for each individuat subject. Grading scales are from -4 to +4 as follows:
• Example sunscreen formulations are prepared according to the methods described herein with the following ingredients:
• Prolipid 141 2.0 - 7.0 Ingredient Amount, % w/w
• Vitamin E 0.01 -3.0
• Disodium EDTA 0,01 - .20

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